IL-17F Gene Polymorphisms Research Articles

Allelic, Genotypic, and Haplotypic Analysis of Cytokine IL17A, IL17F, and Toll-like Receptor TLR4 Gene Polymorphisms in Metabolic-Dysfunction-Associated Steatotic Liver Disease: Insights from an Exploratory Study.

(1) Background: Interleukin 17 (IL17) and toll-like receptor 4 (TLR4) elevate the risk of metabolic and liver diseases. (2) Methods: This study's objective was to explore the association of IL17 and TLR4 gene polymorphisms with MASLD susceptibility and test their effect on serum IL17 and TLR4 levels. A total of 43 patients with MASLD (MASH/MAFL) and 38 healthy individuals were genotyped for IL17F-A7488G, IL17A-G197A, TLR4-Asp299Gly, and TLR4-Thr399Ile polymorphisms using PCR-RFLP. ELISA methods determined IL17F, IL17A, and TLR4 serum levels. (3) Conclusions: Patients carrying the variant genotypes (A/G + G/G) of IL17-A7448G (OR = 5.25), (G/A + A/A) of IL17-G197A (OR = 10.57), (Asp/Gly + Gly/Gly) of TLR4-Asp299Gly (OR = 3.52), or (Thr/Ile + Ile/Ile) of TLR4-Thr399Ile (OR = 9.87) had significantly increased odds of MASH. Genotype (G/A + A/A) of IL17-G197A was significantly associated with the odds of MAFL (p = 0.0166). Allele A of the IL17-G197A polymorphism was significantly related to increased odds of MAFL (OR = 4.13, p = 0.0133). In contrast, allele A of IL17-G197A (OR = 5.41, p = 0.008), allele Gly of TLR4-Asp299Gly (OR = 3.19, p = 0.046), and allele Ile of TLR4-Thr399Ile (OR = 6.94, p = 0.008) polymorphisms were significantly related to an increased risk of MASH. Allele A of IL17A-G197A, allele Gly of TLR4-Asp299Gly, and allele Ile of TLR4-Thr399Ile gene polymorphisms were significantly associated with the increased odds of MASLD. In patients with MASLD, we found significant influence from the IL17A-G197A gene polymorphism on IL17F levels (p = 0.0343).

Role of Interleukin-17F Gene Polymorphism in Susceptibility to Acute Myeloid Leukemia: Relation to Serum Level of IL-17

Abstract Background The pathogenesis of acute myeloid leukemia (AML) is complex and not fully understood. A variety of interleukins have been shown to regulate the survival, growth, and apoptosis of leukemia cells. The IL-17 family includes interleukin-17F [rs763780; A7488G]. The IL-17F rs763780 polymorphism inhibits the wild-type IL-17F's activity and raises tumor susceptibility contributing to the emergence of certain tumor types including AML. Objectives This work aimed to study the relation between IL-17F gene polymorphism and susceptibility to AML and evaluated IL-17 plasma levels in AML with different IL-17F genotypes. Results There was no statistically significant difference in the distribution of different IL-17F genotypes between cases and controls. While the statistical comparison between both groups showed a significant difference with p-value <0.001 regarding IL-17 plasma level being higher in the case group with cutoff value >35 ng/L. Conclusion We concluded that IL-17 gene polymorphism doesn’t increase susceptibility to AML in Egyptian adults. IL-17 plasma level is an excellent diagnostic biomarker in AML patients.

IL-17F gene polymorphism in pulmonary tuberculosis

This study was investigated tuberculosis (TB) patients in an Iraqi population to look at the association between TB development and polymorphisms in the interleukin-17F gene. From January 2017 to April 2017, the study's population included 40 controls and 80 patients with tuberculosis. The IL-17F serum level was assayed using the ELISA technique. Genotyping analyses of IL-17F rs763780 gene were analysed using QRT-PCR for polymorphism. Males outnumbered females (58% vs. 42%) in TB cases. Serum levels of the IL-17F old cases (OC) group have decreased significantly (85.2±109.2pg/ml vs. 194.5±160.0pg/ml), than recently diagnosed (RD) group. The distribution of IL-17F rs76380 genotype was found to be in Hardy-Weinberg equilibrium in OC group and control. The result showed that T allele was more frequent (93.75%, 92.5%, 95% vs. 6.25%, 7.5%, 5% respectively), insignificantly (P>0.05) than C allele in all groups. In addition, TT genotype was more frequent (90%) insignificantly (P>0.05), than genotype TC (7.5%, 5%, 10%) and CC (2.5%, 5%, 0%) among groups of the study. There were insignificant associations between the IL-17F rs763780 gene polymorphism and risk of tuberculosis.

Association of IL-17F Gene Polymorphism and Its Serum Level with SARS-CoV-2 Infection.

Although multiple studies have addressed the clinical outcomes of coronavirus disease, little data exist regarding the defi- nition of immune and inflammatory profiles associated with this infection. Its clinical manifestations often worsen in association with hypercytokinemia (elevated interleukin 8 and interleukin 17). We conducted this research to elucidate the effect of interleukin 17 levels and interleukin 17F gene polymorphism on the severity and outcomes of coronavirus disease. Ninety patients with confirmed coronavirus disease and 30 healthy controls were enrolled. Coronavirus disease cases were classified into nonsevere, severe, and critical according to the World Health Organization definition. Approximately 10 mL peripheral blood sample was collected from all patients and controls by venipuncture in-plane and ethylenediaminetetraacetic acid tube. Enzyme-linked immunosorbent assay kits were used for calculating serum interleukin 17 levels, whereas real-time polymerase chain reaction was used for genotyping using the 5'-nuclease allelic discrimination assay for single nucleotide polymorphisms genotyping. As regards interleukin 17 levels, there was a significant elevation of interleukin 17 in coronavirus disease cases compared to control healthy persons (P < .001). Moreover, serum interleukin 17 levels tended to be significantly higher with increased disease sever- ity (P = .004). Patients with critical diseases expressed a significant rise of interleukin 17 compared to severe (P = .03) and nonsevere cases (P = .02). We noted no significant difference between the critical, severe, and nonsevere cases regarding different interleukin 17F genotypes. Coronavirus disease is associated with elevated levels of interleukin 17, which tended to be considerably higher with disease severity. However, different interleukin 17F genotypes do not affect either the predisposition or the severity of coronavirus disease.

P202 IL-17F gene polymorphisms in cystic fibrosis patients: influence on plasma cytokine levels and mortality rate

The aim of the study was to investigate mortality rate and plasma cytokine concentrations in cystic fibrosis (CF) patients with IL-17F gene polymorphisms: rs2397084 (Glu126Gly) and rs763780 (His161Arg).

Interakcija genetskih varijanti IL-17A (rs2275913-G/A) i IL-17F (rs763780 T/C) sa aknama vulgaris

Objective. Acne vulgaris is a prevalent dermatological disorder with a complex etiology that affects pilosebaceous units and manifests both as inflammatory and noninflammatory skin conditions. The present preliminary study was aimed at evaluating the expression of IL-17A and IL-17F gene polymorphisms in acne vulgaris patients and their relationship to the severity of the condition. Methods. Sixty acne vulgaris patients and 60 healthy individuals (control group) were recruited for the study. Demographic information was obtained from the participants. Also, blood samples were collected and used to isolate DNA. The detection of IL-17A and IL-17F gene polymorphisms was assessed using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results. There was no significant (p &gt; 0.05) difference between patient and control groups in the correlation between the IL-17A gene polymorphism and acne vulgaris disease in all codominance and recessive modes, but the AA and G/A genotypes can be regarded as risk factors (OR = 2.77 and 2.19, respectively) concerning the etiological fraction (EF = 0.346 and 0.331, respectively). Also, there was no statistically significant (p = 0.275) difference between the two groups in terms of the genotypes and allele frequencies for the IL-17F SNP. However, the risk analysis revealed that the CC (OR = 3.42) and T/C genotypes (OR of 1.37) may be taken into account as risk factors and etiological fractions for acne vulgaris. Conclusion. This preliminary study suggests that AA and G/A genotypes in IL-17A and CC and T/C genotypes in IL17F may be risk factors for acne vulgaris.

Detection of IL-17A and IL-17F gene polymorphism in recurrent and disseminated pityriasis versicolor: a case-control study

Recurrent and disseminated pityriasis versicolor (RDPV) is a common clinical entity, characterized by its recurrent and disfiguring nature. Studies demonstrated host genetic variations in the immune response, especially the role of IL-17 in antifungal immunity. This study aimed to detect whether IL-17A and F gene polymorphisms are found in cases of RDPV. It included 100 cases of RDPV and 100 age and sex matched controls, from which EDTA blood samples were taken for single-nucleotide polymorphism analysis. IL-17A (rs2275913) and F (rs763780) were associated with a significantly increased incidence of developing RDPV. IL-17A and F gene polymorphism could be implicated as a risk factor for the development of RDPV.

Влияние однонуклеотидных полиморфизмов гена IL-17F на выживаемость пациентов с муковисцидозом

Цель работы состояла в исследовании влияния аллельных полиморфизмов гена IL-17F rs2397084 (Glu126Gly) и rs763780 (His161Arg) на выживаемость пациентов с муковисцидозом. В исследовании принимали участие 82 пациента. Все участники исследования находились на активном диспансерном наблюдении, регулярно (каждые 3-6 месяцев) обследовались и получали антибактериальную терапию. Частоты аллелей A и G полиморфизма rs2397084 в группе обследованных пациентов составили 90,2 % и 9,8 % соответственно. Частоты аллелей A и G полиморфизма rs763780 были равны 92,1 % и 7,9 %. В зависимости от генотипа пациенты были разделены на 2 группы. Группа 1 состояла из пациентов с распространенным генотипом AA-AA (rs2397084-rs763780; n=55). Группа 2 включала носителей одного или нескольких аллелей G (n=27). Анализ демографических данных показал, что группы пациентов не различались по возрасту, полу, а также по количеству носителей мутации F508del. За период с 2015 по 2020 гг. в группе 1 умерли 14 пациентов, в группе 2 все пациенты остались живы. Таким образом, выживаемость в группах 1 и 2 составила, соответственно, 74,5 и 100 % (p=0,0035, точный критерий Фишера). Анализ кривых Каплана-Майера показал, что общая выживаемость пациентов первой группы была статистически значимо ниже, чем соответствующий параметр в группе 2 (р=0,0026, Log-Rank Test). Анализ состава микробиома дыхательных путей выявил в группе 1 существенное преобладание пациентов с хронической колонизацией Burkholderia cepacia complex: 22 vs 1 пациент в группе 2 (χ2 = 11,82, p = 0,0006; OR 17,33 [95% CI 2,19-137,21]). Таким образом, повышенная смертность больных муковисцидозом с распространенным генотипом AA-AA связана с высокой частотой развития хронической инфекции Burkholderia cepacia complex. Для получения достоверных данных о рисках заражения Burkholderia cepacia complex и неблагоприятном исходе заболевания необходимо увеличить количество обследованных пациентов. The aim of this study was to evaluate effects of IL-17F gene polymorphisms, rs2397084 (substitution of glutamic acid (GAG) for glycine (GGG) at position 126; Glu126Gly) and rs763780 (substitution of histidine (CAT) for arginine (CGT) at position 161; His161Arg) on the cystic fibrosis (CF) patients mortality rate. The study involved 82 patients who were regularly examined (every 3-6 months) and received antibiotic therapy. The frequency of IL-17F (rs2397084) A and G alleles was 90.2% and 9.8%, respectively. The frequency of IL-17F (rs763780) A and G alleles was 92.1% and 7.9%, respectively. The patients were divided into two groups. Group 1 included individuals with common AA-AA genotype (n=55). Group 2 included carriers of one or more minor G alleles (n=27). The patients of two groups did not differ in age, sex, or number of F508del mutation carriers. At the same time, there were 14 dead patients in group 1, whereas all patients from group 2 were alive. Thus, survival in groups 1 and 2 was 74.5% and 100%, respectively (p=0.0035, Fisher’s exact test). Analysis of the Kaplan-Meier curves showed that the overall survival of patients in the group 1 was significantly lower than the corresponding parameter in the group 2 (p=0.0026, Log-Rank Test). Repeated microbiological studies of sputum samples revealed a significant predominance of patients with chronic colonization of the Burkholderia cepacia complex (Bcc) in this group: 22 vs 1 patient in group 2 (χ2 = 11.82, p = 0.0006; OR 17.33 [95% CI 2.19-137.21]). Thus, increased mortality rate in CF patients with common AA-AA genotype is associated with a high incidence of chronic Bcc infection. Further investigations with increased number of participants are needed to estimate more accurately the true risks of Bcc infection and poor outcomes in CF patients with different IL-17F gene polymorphisms.

Association of rs4711998 of IL-17A, rs2275913 of IL-17A and rs763780 IL-17F gene polymorphisms with non-segmental vitiligo in a Mexican population.

Vitiligo is the most common depigmenting disease characterized by achromic macules due to selective loss of melanocytes. The pathogenesis remains poorly elucidated, and multiple hypotheses exist regarding its pathogenesis. Evidence suggests that stress on melanocytes can result in activation of the immune system, and involvement of both activated cluster of differentiation (CD8+) cytotoxic and CD4+ T cells in the dysfunction, depigmentation, and apoptosis of melanocytes. Recent studies show that the interleukin 17 (IL-17) axis plays a central role in the pathogenesis of the disease. IL-17 is an important regulatory effector cytokine in this pathway. The aim of this study was to evaluate the association of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) with vitiligo in a Northeastern Mexican population. This was a case-control study and included 116 patients with vitiligo and 116 control subjects. Genotype characterization of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A p ≤ 0.05 was considered significant. It was observed that the combination of the genotypes GG/GA for IL-17F rs763780 (7488A/G) was associated with an increased risk for the development of vitiligo (OR 2.0943, 95% Cl 1.2375-3.5445, p = 0.0056). Regarding IL-17A rs4711998 (-832A/G) and IL-17A rs2275913 (-197G/A) genotyping, no association with vitiligo development was found. In conclusion, the SNP rs763780 in the IL-17F gene appears to be a risk factor for vitiligo development in this Mexican population and it may be useful in future studies, especially for the development of new therapies.

IL-17F gene polymorphism (7488T/C, rs763780) in Egyptian patients with SLE

IL-17F gene polymorphism (7488T/C, rs763780) in Egyptian patients with SLE

The role of heterodimer IL-17-A/F in atopic dermatitis.

The importance of multifactorial dysregulation in immune response is well recognised in atopic dermatitis (AD). Th17 family cytokine IL-17 (IL-17A-F) is of significance in both acute and chronic phase of AD. We analysed the differences between serum levels of IL-17A/F and IL-17A, IL-17-F, IL-13, IL-4, association of rs2275913 IL-17A and rs763780 IL-17F gene polymorphisms in paediatric AD patients and control subjects. We assessed 30 children with AD and 30 healthy patients aged 2-12 years. Eczema Area and Severity Index, Investigator Global Assessment and Scoring Atopic Dermatitis scales were used to analyse the severity of skin lesions in AD patients. Genotyping was performed using PCR and the serum concentrations of IL-17A/F, IL-17A, IL-17F, while IL-13 and IL-4 interleukins were determined by enzyme-linked immuno-sorbent assays (ELISA). The revised median assessment scoring in disease severity showed that the studied AD population had a moderate course of the disease. The obtained results indicated elevated plasma levels of IL-17A/F and IL-17-13 in AD patients with no statistically significance of IL-17A, IL-17F and IL-4 compared to controls. AD duration was positively correlated with IL-13 levels and negatively with IL-17A/F (p < 0.05). Moreover, there was no significant difference between case and control groups in the frequency of genotypes and alleles at rs2275913 IL-17A and rs763780 IL-17F polymorphisms (p > 0.05). This study demonstrates increased levels of IL-17A/F in atopic patients, which is positively correlated with severity of the disease and the early phase of the disease. These results highlight a functional role of this cytokine in the pathogenesis of AD in paediatric patients.

Association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis.

Psoriasis (Ps) is a chronic dermatosis characterized by erythematous-squamous plaques derived from an inflammatory response. The effect of polymorphisms in the genes that encode the members of the IL-17 family and their receptors has been studied to find an association with the susceptibility to Ps. However, the findings have not been conclusive. To describe the association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to Ps. A systematic review was conducted using the PubMed and Scopus databases to identify studies that evaluated the association between IL-17A, IL-17F, and IL-17RA gene polymorphisms and Ps susceptibility. This meta-analysis included reports published until June 2021. Heterogeneity was assessed using Cochran's Q-statistic test and I2 statistics. The associations between polymorphisms and Ps susceptibility were determined by pooled OR with a 95% CI. Fifteen studies were included. The frequency of the T allele of the IL-17F rs763780 polymorphism was significantly lower in patients with vulgar Ps (OR = 0.732, p = 0.026). The TT genotype of the IL-17F rs763780 polymorphism was significantly associated with a decreased frequency in individuals with Ps and psoriatic arthritis (PsA) (TT:TC + CC OR = 0.664, p = 0.046). Regarding IL-17RA polymorphisms, the AG genotype of the rs4819554 polymorphism showed a near-significant decrease in psoriasis risk compared to the GG genotype (AG:GG OR = 0.604, p = 0.050). Other polymorphisms in IL-17A, IL-17F and IL-17RA showed no association with Ps. The T allele and TT genotype of the IL-17F rs763780 polymorphism may be associated with a decreased risk of psoriasis. Therefore, the implications of this variant on psoriasis pathogenesis and treatment require further investigation.

Il17A (rs2275913 G&gt;A) and IL17F (rs2397084 T&gt;C) gene polymorphisms: relation to psoriasis risk and response to methotrexate

Background IL17F rs763780 polymorphism results in substitution of histidine to arginine at amino acid 161, leading to upregulation of IL17F and increased propensity to autoimmune diseases. The single nucleotide polymorphism rs2275913 (G197A) involves a substitution of the guanine by an adenine nucleotide base in IL17A gene promotor which plays a key role in regulation of cytokine transcription. The relation of IL17 polymorphisms however to psoriasis risk and response to methotrexate has not been previously studied in Egyptians. Objective To study the relation of IL17A (rs2275913 G>A) and IL17F (rs2397084 T>C) polymorphisms to psoriasis risk and assess their predictive role regarding response to methotrexate. Patients and methods The study was conducted in two phases. First, a case–control study including 100 patients with chronic plaque psoriasis and 100 healthy control patients was conducted for IL17A (rs2275913) and IL17F (rs2397084) polymorphisms by real-time PCR. Second, a cohort study was adopted where the patients with psoriasis were treated with methotrexate weekly intramuscularly (0.6 mg/kg) for 12 weeks and followed for clinical response. Results IL17F TT genotype was more frequent in patients (87%) than controls (68%), whereas TC genotype was more frequent in controls (32%) than patients (13%). TT genotype was associated with increased risk of psoriasis, whereas the TC allele was associated with a decreased risk. There was no significant difference regarding IL17A GG, GA, and AA genotype frequencies between patients and controls. Psoriasis area and severity index greater than or equal to 75% was achieved in 22 patients (73.3%) with the TT genotype and eight patients (26.7%) with TC genotype (P=0.019). Conclusion IL17F (rs2397084 T>C) TT genotype could be considered a susceptibility marker in Egyptian patients. Psoriatic patients with TT genotype and T allele of IL17F (rs2397084 T>C) are likely to show a better response to methotrexate.

Association between IL-17A and IL-17F gene polymorphism and susceptibility in inflammatory arthritis: A meta-analysis

ObjectivesThe association between Interleukin (IL)-17A and IL-17F gene polymorphism with inflammatory arthritis were inconsistent among previous studies. This meta-analysis aimed to determine the association between IL-17A and IL-17F gene polymorphism with ankylosing spondylitis (AS), osteoarthritis (OA) and rheumatoid arthritis (RA). MethodsWe searched Medline up to August 2019. The summary Odds Ratio (OR) with corresponding 95% confidence intervals (CIs) was calculated to evaluate the relationship between IL-17A and IL-17F gene polymorphism with genetic susceptibility of AS, OA and RA. ResultsA total of 19 studies with 5298 cases and 5675 healthy controls were included. There were significant associations between rs2275913 G allele with OA, RA susceptibility (P < .05) but not AS. Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to AS and OA in Caucasian populations (P < .001) but not Mongolians. A significant association between rs763780 and RA susceptibility was detected in Caucasian populations (P < .05). ConclusionIL-17F gene rs763780 C allele confers increased risk of inflammatory arthritis in Caucasians; IL-17A gene rs2275913 G allele are protective for OA susceptibility in Mongolians. More well-designed studies with larger sample size are needed to elucidate the role of IL-17A gene rs2275913 G allele in inflammatory arthritis, especially AS.

Investigation of IL-17F (rs763780) gene Polymorphisms in cases with Iraqi renal failure patients

Renal failure (RF) is common disease, it is decrease of kidney function, glomerular filtration rate (GFR) this use to estimate the kidney function reduction usually is less than 60 mL / min, depending on global Burden of Disease, and the disease is ninth cause of death in the world, According to the global Burden of Disease. Our study is investigated in the relationship between IL-17F (rs763780) genes polymorphic variants in renal failure patients in Iraq. This study was accompanied around Iraqi renal failure patients, the period from February to November 2018. This study included 70 patients from Abn-Sina Center for dialysis and kidney disease, and 30 healthy controls. Tetra-primer ARMS-PCR is rapid, effective and developed assay used our study for studying in genotyping polymorphism of IL-17F (rs763780) genes. Result of our report including the correlation between the genotypes of IL-17F (rs763780) and the incidence of renal failure, as the results show a non-marked difference between patients and controls when genotype T/T (OR = 0.75). Also, no significant difference between patients and control when genotype C/C (OR = 0.85), while the genotype T/C (OR = 2.23) show important difference between control and patients more than two times. In conclusion, IL-17F play an essential role as pro-inflammatory cytokine in renal failure patients and development disease.

Evaluation of the relationship of IL17A and IL17F gene polymorphisms with the response to treatment in psoriatic patients using biological drugs: case-control study in patients in eastern Turkey

IntroductionIL-17A and IL-17F cytokines have important roles in the pathogenesis of psoriasis.AimTo examine the associations of IL-17A rs2275913 and IL-17F rs763780 variants with the development of psoriasis and whether these polymorphisms affect the responsiveness of biological agents.Material and methodsIn our case-controlled study, which included 83 psoriatic patients who were treated with different biological agents and 69 healthy controls, we genotyped IL-17A rs2275913 and IL-17F rs763780 variants using TaqMan probes.ResultsWe did not observe statistically significant changes in genotype frequencies of IL-17A rs2275913 (p = 0.922) and IL-17F rs763780 (p = 0.621) variants between patient and control groups. Although we did not find any association between these polymorphisms and the development of psoriasis, statistical analyses showed that individuals with the IL-17A AA genotype had shorter disease duration (9.09 ±6.82, p = 0.020) and AA genotype frequency was higher in patients who used single conventional treatment (34.6%; p = 0.025). IL17A/rs2275913 variant in terms of disease duration, it was observed that individuals with AA genotype had a shorter disease duration (less than 10 years) (p = 0.009). For patients with PASI90 and PASI100 response, the IL-17A AA genotype was significantly higher (p = 0.015). On the other hand, we did not detect any statistically significant correlation between variants and response to biological agents.ConclusionsAccording to our results, we may suggest that rs2275913 variant seems to be associated with disease duration, use of single conventional treatment and responsiveness of PASI90 and PASI100 however both variants have no effect on the susceptibility to psoriasis in the population of Eastern Turkey.

Association between the polymorphism of IL-17A and IL-17F gene with knee osteoarthritis risk: a meta-analysis based on case-control studies

BackgroundKnee osteoarthritis is a joint disease which is characterized by degeneration of articular cartilage and subsequent subchondral bone changes. Polymorphisms of IL-17A/F gene were the recognized candidate genes associated with knee osteoarthritis risk although the results were conflicting. The aim of this study was to determine whether IL-17A(rs2275913) and IL-17F(rs763780) polymorphisms confer susceptibility to knee osteoarthritis.MethodLiterature search was performed in PubMed, Medline, Cochrane Library, Web of science, Embase, and Google Scholar (last search was updated on June 20, 2019), and assessing this association was performed by calculating odds ratios with 95% confidence intervals. Statistical heterogeneity was quantitatively evaluated by using the Q statistic with its p value and I2 statistic.ResultSix case-control based studies were included involving IL-17A(rs2275913) (2134 cases and 2306 controls) and IL-17F(rs763780) (2134 cases and 2426 controls). The overall analysis suggested that the A allele of the rs2275913 polymorphism, and the C allele of the rs763780 polymorphism in the IL-17 gene may increase the risk of OA. However, subgroup analysis revealed that no association between IL-17A(rs2275913) gene and knee OA risk was found in Caucasian population.ConclusionsThis meta-analysis revealed that the IL-17A(rs2275913) gene polymorphisms may increase the risk of knee OA in Asians, and the IL-17F(rs763780) gene polymorphisms may increase the risk of knee OA both in Asians and Caucasians. However, because of the limitations of the present study, additional larger studies are needed to confirm our findings in the future.

IL17A and IL17F genes polymorphisms are associated with histopathological changes in transplanted kidney

BackgroundInterleukin 17 is a proinflammatory cytokine involved in immune response after allograft transplantation. IL-17 family of proinflammatory cytokines includes IL-17A and IL-17F. Previous studies have demonstrated that the rs2275913 IL17A and the rs11465553 IL17F gene polymorphism are associated with kidney allograft function. Because of the association between these polymorphisms and post-transplant immune response, we assume that these single nucleotide polymorphisms may affect morphological structure of transplanted kidney.The aim of this study was to examine the association of rs2275913 IL17A and rs2397084, rs11465553 and rs763780 IL17F gene polymorphisms with histopathological changes in transplanted kidney biopsies such as: glomerulitis, tubulitis, arteritis, cell infilitration and fibrosis.MethodsThe study enrolled 82 patients after renal graft transplantation in whom a kidney biopsy was performed because of impaired graft function. The rs2397084 T > C (Glu126Gly), rs11465553 G > A (Val155Ile) and rs763780 T > C (His167Arg) polymorphisms within the IL17F gene and the rs2275913 A > G (− 197 A > G) polymorphism within the IL17A gene promoter were genotyped using TaqMan genotyping assays on a 7500 FAST Real-Time PCR System (Applied Biosystems, USA).ResultsThere was a significant association between the rs2275913 IL17A gene polymorphism and the grade of tubulitis, which was more severe among patients with the A allele, compared to recipients with the GG genotype (GG vs. AG + AA, P = 0.02), and with the grade of arteriolar hyaline thickening and mesangial matrix increase, which were more severe among patients with the G allele compared to recipients with the AA genotype (AA vs. AG + GG, P = 0.01 and P = 0.04, respectively). Tubular atrophy and interstitial fibrosis were more severe among individuals with the C allele at the rs763780 IL17F gene polymorphism (TT vs. TC, P = 0.09 and P = 0.017, respectively). However, it should be taken into account that the statistical significance was achieved without correction for multiple testing, and no significant association would remain significant after such correction.ConclusionsThe results of this study may suggest a possible association between the rs2275913 IL17A and rs2275913 IL17A gene polymorphisms and some histopathological changes in transplanted kidney biopsies.

The combined effect of IL-17F and CCL20 gene polymorphism in susceptibility to multiple sclerosis in Egypt

BackgroundLevels of CCL20 and its CCR6 receptor are elevated in many autoimmune diseases which help in the recruitment of T helper (Th17) cells to site of inflammation. ObjectivesDetermine the value of single nucleotide polymorphism of CCL20 (rs6749704) and IL-17F (rs763780) genes and their concomitant effect on the serum CCL20 level and susceptibility to MS in Egyptian patients. Subjects and methodsBlood samples were collected from 83 patients and 95 healthy subjects. Serum levels of CCL20 were measured by ELISA. The DNA was analyzed for rs6749704 and rs763780 using Genotyping Taqman assay. ResultsThe mean serum levels of CCL20 in the MS group were significantly higher than healthy group (P < 0.001). Frequencies of CT genotype of rs6749704 in CCL20 gene and C allele in MS patients were significantly higher compared to controls. Also significant increase of rs763780 in IL-17F gene was detected in MS patients. Concomitant polymorphism in both genes in MS patients showed an increase risk to MS rather than individual locus. ConclusionCCL20 may play an important role in the pathogenesis of MS. Both allelic variation of (rs6749704) within CCL20 gene and (rs763780) within IL-17F gene can be considered risk factor for development of MS in Egyptian patients.

IL-17A gene polymorphism at position G197A and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multi-systemic disorder with various clinical manifestations. Lupus is a multifactorial autoimmune disease resulting from complex gene-environment interactions. IL-17 is a pro-inflammatory cytokine secreted by Th-17 cells, and IL-17A and IL-17F are two predominant members of this family. The present study assessed the association of IL-17F (rs763780) gene polymorphism with SLE. A total of 102 SLE patients and 141 healthy subjects were enrolled in this case-control study. Genotyping was done using the PCR-RFLP technique. The results were analyzed using SPSS software. Results showed a borderline relationship between the heterozygote genotype (AG) and a reduced risk of SLE (OR: 0.31, 95% CI: 0.09-1.0, P=0.05). The A allele was also shown as having a protective effect on SLE susceptibility (OR: 0.68, 95% CI: 0.46-1.0, P=0.05). No association was observed between the genotypes of the IL-17F gene polymorphism and the risk of SLE (P>0.05). In conclusion, it seems that the IL-17A gene may be involved in the pathogenesis of SLE.